The applicant's broad, long-term objective is to better understand the pathophysiological mechanisms of epilepsy, so that epileptic patients (in human and veterinary medicine) can be diagnosed and treated more effectively. The goal of the proposed project is to investigate the mechanisms underlying temporal lobe epilepsy by studying the hippocampus of the kainic acid-treated rat, which is a widely accepted model of temporal lobe epilepsy. The general hypotheses of this project are that kainic acid-treatment causes reduced excitatory synaptic drive to inhibitory interneurons, resulting in less inhibition of CA1 pyramidal cells, and that kainic acid-treatment causes reorganization of granule cell and CA 1 pyramidal cell axon collaterals, leading to recurrent excitatory circuits. Furthermore, it is hypothesized that these changes produce hyperexcitability and reduce the seizure threshold in the hippocampus. It would be difficult, or impossible, to adequately address these issues using the hippocampal slice technique; therefore, an in vivo intracellular recording and labeling preparation will be used. The specific aims of this project are to compare kainic acid-treated and control rats to: (1) identify the source of regenerative afferent fibers to CA1 pyramidal cells; (2) examine the intrinsic and synaptic physiology of CA1 pyramidal cells and dentate granule cells; (3) determine whether there is long-term hyperexcitability and reduced seizure threshold that correlates with hilar neuron loss and mossy fiber sprouting in the dentate gyrus; (4) describe quantitatively the extent of mossy fiber sprouting and identify the postsynaptic targets of the axon sprouts; and (5) investigate the intrinsic and synaptic physiology and axon projections of inhibitory interneurons.